This is a renewal application of an Interdepartmental Stroke Program at the MGH, now in its 5th year, involving the departments of Radiology (Neuroradiology), Neurology, Neurosurgery, Pathology (Neuropathology) and Medicine. During the first four years of the grant, emphasis has been on the development of methods to carry out measurements of cerebral blood flow and metabolism by non-invasive techniques utilizing radioactive indicators such as 133 Xenon and cyclotron produced short-lived isotopes, chiefly 15O2, 13N, and 11C. A Xenon CBF laboratory has been developed and will be heavily utilized in succeeding years of the grant (if approved). The technology of imaging with positron emitters has now reached a certain level of sophistication and results obtained through the application of these techniques can be expected in the next several years. In our future efforts, emphasis will be on studies concerning the pathophysiology and therapy of acute stroke. To this end we plan to utilize the technology already developed in order to gather data in a sufficiently large number of patients to determine the actual value of 133 Xenon monitored cerebral blood flow in the management of the stroke patient as well as on the utility in the clinical situation of positron emitters to study cerebral blood flow and metabolism including oxygen glucose and deoxiglucose. Other investigations include the effect of 4 major neurotransmitters on local cerebral blood flow in ischemic areas, electron microscopic studies of the arterial walls in spastic cerebral vessels in animals, and investigation of the rate of formation and the fate of platelet thrombi tagged with a radioactive indicator. Our therapeutic efforts include the use of nitroglycerine to relieve cerebral arterial spasm, the use of a proton beam to treat inoperable arteriovenous malformations, and the study of factors affecting recovery from aphasia; the latter to be used as a basis to assess results of any treatment program.